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Biomedical subjects

R Saunders

Publications and source records attributed to R Saunders.

At least 73 records · Page 4Linked to original sources

A cluster of Pallister-Hall syndrome cases, (congenital hypothalamic hamartoblastoma syndrome).

We report on three infants with hand anomalies and congenital hypopituitarism. In two of the cases, a hypothalamic tumor was found; the third infant died without postmortem brain studies. Family history in the first case suggested possible familial recurrence; the mother's sister had died at 17 hr of age with polydactyly, microglossia, and flat nasal bridge (no autopsy done). Our second case was born by cesarean section after a pregnancy complicated by extremely low maternal estriols. At birth, hypopituitarism was diagnosed, a cranial CT scan was read as normal, and hormonal replacement was begun with thyroxine, hydrocortisone, and growth hormone. At 11.5 mo of age she developed seizures; and a repeat CT scan showed a mass extending beneath the hypothalamus. This tumor was removed surgically at 12 mo, the first successful treatment of this disorder. Our third possible case had a bifid epiglottis, hypopituitarism, and hand anomalies. A CT scan at birth failed to reveal a mass in the hypothalamus. This child died from complications of untreated hypopituitarism, and no neuropathology studies were done. These three cases were conceived between March 10th and April 17th in three different years in three geographically contiguous counties of Vermont. Clustering in time and space and possible familial recurrence, in one of these cases, suggest a possible gene/environment interaction.

Abnormalities, Multiple↗

The effects of thiazide diuretics upon plasma lipoproteins.

In a double-blind, placebo-controlled, crossover study in 16 hypertensives, 4 weeks of 50 mg hydrochlorothiazide twice daily, caused significant elevations in total plasma cholesterol, high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol, very low density lipoprotein (VLDL)-cholesterol and triglycerides. Significant elevations in fasting plasma glucose and in plasma insulin were observed, but no correlation between individual lipid elevations and either glucose or insulin elevations was apparent. The metabolic effects developed within 2 weeks, and dissipated within 4 weeks. Changes induced within 4 weeks of treatment with hydrochlorothiazide were unaltered at 6 months. Hydrochlorothiazide induces elevation of all lipoprotein cholesterol fractions and VLDL-triglyceride. However, as the important ratio between LDL- and HDL-cholesterol is unchanged, coronary risk may be unchanged.

Adult↗

Comparative double-blind trial of the effectiveness and antigenicity of semisynthetic human insulin and purified porcine insulin in newly treated diabetic subjects.

A double-blind comparative trial of the effectiveness and antigenicity of semisynthetic human insulin (Novo) and highly purified (Monocomponent) porcine insulin was performed over a 12 month period in 20 diabetic subjects newly treated with insulin. Human insulin was shown to be indistinguishable from porcine insulin of comparable purity with respect to plasma glucose and glycosylated hemoglobin levels and insulin dose requirements. Human insulin was no less antigenic than porcine insulin; significant IgG-associated insulin binding activity was detected in six of the ten patients in the human insulin treated group and four of the ten patients in the porcine insulin treated group. In all patients, the binding activity was of low capacity. No adverse reactions to human insulin were noted. It is concluded that semisynthetic human insulin, like purified porcine insulin, is safe and effective. Although there may be advantages for human insulin in the setting of insulin allergy, this study does not indicate that human insulin has advantages over purified porcine insulin with respect to elicitation of antibodies of the IgG class.

Adult↗

Effects of intravenous infusion of esmolol and propranolol on biventricular performance at rest and during exercise as assessed by quantitative radionuclide angiography.

This double-blind, randomized, crossover study examined the effects of intravenous infusion of esmolol (a new ultra-short-acting beta-receptor blocking agent) and propranolol on cardiovascular performance at rest and during peak upright exercise in 15 patients. Biventricular function was assessed by means of first-pass radionuclide ventriculography with a computerized multicrystal camera. At rest, significant treatment differences between esmolol and propranolol vs baseline were found for the heart rate, systolic blood pressure, double product, left ventricular ejection fraction (EF), systolic blood pressure to end-systolic volume ratio, cardiac index and right ventricular EF. During exercise, significant treatment differences were also found for the heart rate, systolic blood pressure, double product, right ventricular EF and cardiac index. The mean baseline measurements were higher than the mean treatment measurements, but no significant differences were found between mean esmolol and mean propranolol measurements at rest and during exercise except for the exercise systolic blood pressure, which was lower during esmolol infusion. The magnitude of drug effect was greater at the time of exercise than at rest. The blood level of esmolol decreased markedly by 30 minutes after infusion. Esmolol was well tolerated, with no important local, systemic or laboratory abnormalities. Thus, the effects of esmolol on cardiovascular performance at rest and exercise are similar to those of propranolol.

Aged↗

Antiarrhythmic activity of esmolol (ASL-8052)--a novel ultra-short acting beta-adrenoreceptor blocking agent.

In a single-blind, placebo-controlled study, esmolol was administered intravenously to 12 patients with chronic atrial fibrillation. Esmolol produced a significant dose-dependent decrease in the ventricular rate without conversion to normal sinus rhythm in any of the patients. For most patients, a correlation was observed between the blood levels of esmolol and reductions in heart rate. There were no significant adverse effects. We conclude that esmolol is an effective and safe agent for the control of heart rate in patients with supraventricular tachycardia.

Adrenergic beta-Antagonists↗

Effect of short-term infusion of sodium nitroprusside on mortality rate in acute myocardial infarction complicated by left ventricular failure: results of a Veterans Administration cooperative study.

Eight hundred twelve men with presumed acute myocardial infarction and left ventricular filling pressure of at least 12 mm Hg participated in a randomized double-blind placebo-controlled trial to assess the efficacy of a 48-hour infusion of sodium nitroprusside. The mortality rates at 21 days (10.4 per cent in the placebo group and 11.5 per cent in the nitroprusside group) and at 13 weeks (19.0 per cent and 17.0 per cent, respectively) were not significantly affected by treatment. The efficacy of nitroprusside was related to the time of treatment: the drug had a deleterious effect in patients whose infusions were started within nine hours of the onset of pain (mortality at 13 weeks, 24.2 per cent vs. 12.7 per cent; P = 0.025) and a beneficial effect in those whose infusions were begun later (mortality at 13 weeks, 14.4 per cent vs. 22.3 per cent; P = 0.04). Nitroprusside should probably not be used routinely in patients with high left ventricular filling pressures after acute myocardial infarction. However, the results in the patients given late treatment suggest that those with persistent pump failure might receive sustained benefit from short-term nitroprusside therapy.

Aged↗

Thiopental disposition as a function of age in female patients undergoing surgery.

The effect of age on the disposition kinetics of thiopental was studied in 22 lean female patients having a body mass index (weight (kg/height(m)2) less than 30 and whose age ranged between 25 to 83 years. Patients underwent primarily abdominal surgery. A strong positive correlation between age and the apparent volumes of distribution, V beta and Vss, was found (P less than 0.001). No significant relationship was found between total body clearance and age. The elimination half-life (t1/2) of thiopental increased with age, and was primarily a function of volume of distribution. The free or unbound fraction of thiopental in serum (alpha) ranged between 0.168 and 0.276 and was significantly correlated with age (P less than 0.005). Multiple regression analysis indicated that age was the independent variable which contributed most the variability in t1/2, V beta, and Vss. No conclusion can be reached concerning the potential differences in anesthetic induction doses required as a function of age; however, these data suggest that care may be required in the use of a balanced anesthetic technique in the elderly as a result of prolonged elimination.

Abdomen↗

Thiopental disposition in lean and obese patients undergoing surgery.

The effect of obesity on the disposition kinetics of thiopental was studied in seven morbidly obese (age 25 to 46 years) and eight age-matched lean patients (age 25 to 43 years), undergoing primarily abdominal surgery. Based upon total (bound + free) thiopental concentrations, the average (+/-SD) volumes of distribution in the terminal disposition phase and at steady-state (V beta and V ss) were significantly larger in the obese (7.94 +/- 4.55 1/kg and 4.72 +/- 2.73 1/kg, respectively) than in the age-matched lean patients (1.95 +/- 0.63 1/kg and 1.40 +/- 0.46 1/kg, respectively). Clearance of total thiopental, normalized for total body weight was not significantly different between the obese (0.18 +/- 0.081 . h-1 . kg-1) and lean patients (0.21 +/- 0.06 1 . h-1 . kg-1). However, total body clearance not normalized for total body weight was significantly larger in the obese (24.98+/- 14.87 1/h) than in the lean patients (11.86 +/- 3.66 1/h). The elimination half-life of thiopental was significantly longer in the obese (27.85 h) than in the lean patients (6.33 h) and this difference was primarily a function of a larger apparent volume of distribution for thiopental. The unbound fraction of thiopental in serum (range, 17.8 per cent to 27.6 per cent) was not correlated with the degree of obesity. The most appropriate means of comparing intrinsic metabolizing capacity (i.e., normalized vs. non-normalized for weight) between lean and obese subjects remains unresolved.

Abdomen↗

Antibody to hepatitis B surface antigen is not cytotoxic to antigen-secreting hepatocytes.

A continuously growing cell line which produces hepatitis B surface antigen was grown in the presence of antibody to the surface antigen. Antibody from animal and human sources was used. Neither growth rate nor cell morphology was affected and the cells did not inactivate the antibody over a 4-day incubation period. The surface antigen produced was specifically neutralized. These results suggest that hepatic injury occurring in response to hepatitis B virus infection is not mediated by humoral immunity to the surface antigen.

Antibodies, Viral↗

The separation of alpha-2 macroglobulin into five components with differing electrophoretic and enzyme-binding properties.

The alpha-2 macroglobulins from human serum and plasma were isolated by Bio-Gel P-300 and A5m gel filtration. The material showed a single peak on sedimentation velocity ultracentrifugation, a mol wt of 650,000 by sedimentation equilibrium ultracentrifugation, and a major precipitin arc in the alpha-2 macroglobulin region by immunoelectrophoresis against whole human serum. Two bands were observed in the alpha-2 macroglobulin region when acrylamide gel electrophoresis was performed with a pH 8.9 running gel. When a pH 7.8 gel was used, five electrophoretic species were observed. In both cases, the preaddition of stoichiometric amounts of trypsin or chymotrypsin added to alpha-2 macroglobulin resulted in disappearance of slower bands leaving only one band on acrylamide gel electrophoresis patterns. Preparative acrylamide gel electrophoresis separated alpha-2 macroglobulin obtained from Bio-Gel into five closely-spaced species. Separation was sufficiently adequate to show that those species of alpha-2 macroglobulin which bound trypsin and chymotrypsin were represented by slower moving species and that the fastest moving material had lost virtually all of the ability to bind these enzymes. Preparative acrylamide gel electrophoresis of a mixture of alpha-2 macroglobulin-trypsin complex and alpha-2 macroglobulin revealed that the fast moving component was alpha-2 macroglobulin-trypsin complex and that the slower moving material was unbound alpha-2 macroglobulin. The naturally occurring amidase activity of the alpha-2 macroglobulin using benzoylarginine-p-nitroanilide (BAPNA) as substrate was investigated and unlike its trypsin-binding activity, amidase activity was found to be of the same specific activity in all electrophoretic fractions. Binding of trypsin and chymotrypsin to alpha-2 macroglobulin revealed that alpha-2 macroglobulin maximally bound 2 moles of trypsin and 1 mole of chymotrypsin. When the enzymes were added simultaneously there was competition. Chymotrypsin added to alpha-2 macroglobulin before the addition of trypsin prevented all trypsin binding even though only one site was filled with chymotrypsin. These results were explained by the acrylamide gels which showed that 1 mole of chymotrypsin was sufficient to convert all the alpha-2 macroglobulin to a species with the fastest mobility which no longer binds additional enzyme.

Acrylamides↗

[The croup tent].

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Laryngitis↗